ficantly affected IPA Tox pathways in the high exposure chem ically dispersed oil data set were Positive Acute Phase Response Proteins, Aryl Hydrocarbon Receptor Signaling, Cell Cycle, G1 S Checkpoint Regulation, Negative Acute kinase inhibitor ARQ197 Phase Response Proteins, Inhibitors,Modulators,Libraries and Fatty Acid Metabolism. In the larvae exposed to the highest concentration of mechanically dispersed oil, the top IPA Tox list included Negative Acute Phase Response Proteins, p53 Signaling, Liver Prolif eration, Oxidative Stress, and Cholesterol Biosyn thesis. Fishers exact test was used to calculate a p value determining the probability that the associ ation between the genes in the dataset and the IPA Tox pathways was explained by chance alone. In an attempt to identify unique and common mole cules across the gene lists the IPA Compare function was applied.
Additional file 5 shows the associated functions of the top networks as suggested by IPA Core Analysis in significantly affected transcripts in cod larvae exposed to the different exposure treatments. According to the IPA Tox, the unique molecules in both Inhibitors,Modulators,Libraries the CDH and MDH lists encode proteins responding to oxidative stress. NRF2 mediated Oxidative Stress Response topped the list in larvae from the CDH ex posure group, while Oxidative Stress and NRF2 mediated Oxidative Stress Response topped the list in the larvae from the MDH group. These results do not suggest that the two different ways of inducing oil droplets has influenced a major differ ence in affected pathways in the highest exposure con centration groups.
In Inhibitors,Modulators,Libraries the medium concentration groups, molecules unique to larvae exposed to chemically induced oil, LXR RXR Activation topped the list, followed by Positive Acute Phase Response Inhibitors,Modulators,Libraries Pro teins and FXR RXR Activation, while PPARa RXRa Activation topped the MDM group. Molecules common to the two high exposure groups, suggests that either way of inducing dispersed oil affected many of the same pathways as indicated by the IPA Tox lists for the separate exposure groups shown in Table 1. The five most significant Anacetrapib pathways according to the com mon CDH and MDH molecule list were Negative Acute Phase Response Proteins, Aryl Hydrocarbon Re ceptor Signaling, Cell Cycle, G1 S Checkpoint Regulation, Positive Acute Phase Response Pro teins and Cholesterol Biosynthesis.
In the medium sellekchem exposure groups CDM and MDM, many of the same mechanisms as in the high exposure groups were induced in the cod larvae, as suggested by the common molecules, with Cytochrome P450 Panel Substrate is a Xenobiotic topping the IPA Tox list, followed by Aryl Hydrocarbon Recep tor Signaling. This result clearly shows that components in the dispersed oil have triggered mechan isms known to be induced in animals after exposure to hydrocarbon contaminants. Discussion The current microarray analysis suggests that chem ically dispersed oil has lower transcriptomic effect on larvae of Atlantic cod than mechanically dispersed oil, based on the number of significantly affected tran sc